Conformation of cyclo-(D-phenylalanyl-trans-4-fluoro-D-prolyl).
cyclo(D-Phenylalanyl-trans-4-fluoro-D-prolyl), c(D-Phe-D-FPro), was synthesized and its conformation determined both in solution and in the solid state by 1H NMR and X-ray analysis, respectively. In the crystals the 2.5-diketopiperazine (DKP) ring assumes the uncommon conformation, for cyclodipeptides containing Pro residue, of a flattened chair, which seemingly results from a compromise between, on the one hand, the DKP-aromatic intramolecular ring-ring attraction (folding), requiring the C alpha--C beta bond of the Phe to be axial, and, on the other hand, the intrinsic tendency of the Pro residue to have its C alpha--C beta bond equatorial. Unlike the solid state, the 1H NMR data in CDCl3 and C6D6 demonstrate that in both solutions the DKP ring assumes a boat-like shape, typical for the Pro-containing cyclodipeptides, with the equatorial C alpha--C beta bonds in both amino acid residues, which preclude ring-ring folding. A similar conformation was encountered in the closest analog of c(D-Phe-D-FPro), viz, in c(Phe-Pro), both in solution (21, 22, 26) and in the solid state (12). A subtle interplay of intramolecular interactions introduced into a cyclodipeptide by a Pro-type and a Phe-type residue is emphasized.
Ciarkowski
J
J
Institute of Chemistry, University of Gdańsk, Poland.
Gdaniec
M
M
Kołodziejczyk
A
A
Liberek
B
B
Borremans
F A
FA
Anteunis
M J
MJ
D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
D010456:Peptides, Cyclic; C067224:cyclo(phenylalanyl-4-fluoro-prolyl)